title: Fatty acid transport protein expression in human brain and potential role in fatty acid transport across human brain microvessel endothelial cells.
abstract: The blood-brain barrier (BBB), formed by the brain capillary endothelial cells, provides a protective barrier between the systemic blood and the extracellular environment of the CNS. Passage of fatty acids from the blood to the brain may occur either by diffusion or by proteins that facilitate their transport. Currently several protein families have been implicated in fatty acid transport. The focus of the present study was to identify the fatty acid transport proteins (FATPs) expressed in the brain microvessel endothelial cells and characterize their involvement in fatty acid transport across an in vitro BBB model. The major fatty acid transport proteins expressed in human brain microvessel endothelial cells (HBMEC), mouse capillaries and human grey matter were FATP-1, -4 and fatty acid binding protein 5 and fatty acid translocase/CD36. The passage of various radiolabeled fatty acids across confluent HBMEC monolayers was examined over a 30-min period in the presence of fatty acid free albumin in a 1 : 1 molar ratio. The apical to basolateral permeability of radiolabeled fatty acids was dependent upon both saturation and chain length of the fatty acid. Knockdown of various fatty acid transport proteins using siRNA significantly decreased radiolabeled fatty acid transport across the HBMEC monolayer. Our findings indicate that FATP-1 and FATP-4 are the predominant fatty acid transport proteins expressed in the BBB based on human and mouse expression studies. While transport studies in HBMEC monolayers support their involvement in fatty acid permeability, fatty acid translocase/CD36 also appears to play a prominent role in transport of fatty acids across HBMEC.
authors.affiliation: Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Ryan W
authors.initials: RW
authors.lastname: Mitchell
authors.forename: Ngoc H
authors.initials: NH
authors.lastname: On
authors.forename: Marc R
authors.initials: MR
authors.lastname: Del Bigio
authors.forename: Donald W
authors.initials: DW
authors.lastname: Miller
authors.forename: Grant M
authors.initials: GM
authors.lastname: Hatch
mesh_terms: D000465:Algorithms; D000818:Animals; D001693:Biological Transport, Active; D001812:Blood-Brain Barrier / Q000502:physiology; D015153:Blotting, Western; D001923:Brain Chemistry / Q000187:drug effects*; D018955:CD36 Antigens / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D002196:Capillaries / Q000187:drug effects / Q000378:metabolism*; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D050612:Fatty Acid Transport Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D051379:Mice; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D018955:CD36 Antigens; D050612:Fatty Acid Transport Proteins; D005227:Fatty Acids; D034741:RNA, Small Interfering; C493569:Slc27a1 protein, mouse; C493572:Slc27a4 protein, mouse